Chirality is ubiquitous in Nature. One enantiomer of a molecule is often physiologically active, while the other enantiomer may be either inactive or toxic. For example, S-ibuprofen is as much as 100 times more active than R-ibuprofen. R-thalidomide is a sedative, but S-thalidomide causes birth defects. Worldwide sales of chiral drugs in single enantiomeric dosage forms reached $133 billion in 2000, growing at an annual rate of 13%. See, S. C. Stinson, Chiral Pharmaceuticals, Chem. Eng. News, 79(40), 79 (2001). The industrial synthesis of chiral compounds presently utilizes solution-phase, homogeneous catalysts and enzymes.
There have been elegant experiments directed at the production of enantiospecific heterogeneous catalysts in which achiral surfaces are modified by chiral molecules in order to impart enantiospecificity to the surface. It has been shown, for instance, that tartaric acid adsorbed onto both Cu(110) and Ni(110) produces chiral surfaces. See, e.g., M. O. Lorenzo et al., Nature 404 376 (2000) and V. Humblot et al., J. Amer. Chem. Soc., 124, 503 (2002). A. Kuhnle et al., Nature, 415, 891 (2002) reported that cysteine adsorbed on Au(110) from a racemic mixture forms molecular pairs which are exclusively homochiral. Y. Izumi et al., Adv. Catal., 32, 215 (1983) reported that Raney Ni modified with (R,R)-tartaric acid can be used to catalyze the hydrogenation of β-ketoesters, producing the R-product with over 90% enantiomeric excess. Switching the enantiomer of the adsorbate switches the product to the S-isomer. One problem with this approach to heterogeneous catalysis is that the adsorption of chiral modifiers needs to be carefully maintained during the synthesis. See, C. LeBlond et al., J. Amer. Chem. Soc., 121, 4920 (1999).
Another approach to the preparation of chiral heterogeneous catalysts is to use high-index surfaces of single crystals. These high-index surfaces are prepared by slicing a low-index single crystal at an angle. The groups of Gellman and Attard have shown that high-index faces of fcc metals can exhibit chirality due to kink sites on the surface. For example, Pt and Au metal crystals with (643) and ( 64 3) faces are enantiomorphs. See, e.g., C. F. McFadden et al., Langmuir, 12, 2483 (1996); J. D. Horvath et al., J. Amer. Chem. Soc., 123, 7953 (2001); op. cit., 124, 2384 (2002); A. Ahmadi et al., Langmuir, 15, 2420 (1999); G. A. Attard et al., J. Phys. Chem. B. 103, 1381 (1991); op. cit., 105, 3158 (2001). D. S. Sholl et al., J. Phys. Chem. B. 105, 4771 (2001) have proposed a naming and characterization scheme for these chiral metal surfaces. Only the surface of these materials is chiral, because the fcc metals are highly symmetrical and do not have chiral space groups. The (531) surface of Pt has been shown to be enantioselective for the electrochemical oxidation of 1-glucose by A. Ahmadi et al., Langmuir, 15, 2420 (1959). However, there are presently no heterogeneous catalysts that can be used for chiral synthesis on a commercial scale.
Thus, there is a continuing need for enantiospecific heterogeneous catalysts, that are sufficiently stable so that they can be easily separated from the starting materials and products. There is also a need for chiral surfaces that can be used as electrochemical sensors to detect chiral molecules.